ABSTRACT ? Computational and Systems Biology Core The Computational and Systems Biology Core will provide access to advanced data analysis algorithms and pipelines for the entire project. High-quality preprocessed data will be seamlessly integrated from the Omics and Technology Core. Our analysis pipelines will perform all major steps of data analysis, including outlier detection, differential analysis, pathway analysis, and advanced network methods. We will develop methods specifically tailored for multi-compartment omics data in this project, e.g. from blood, gut, and brain. Such novel methods for integrated multi-omics, multi-compartment data will provide a unique readout of AD pathology and allow us to unlock the full potential behind these heterogeneous datasets. Moreover, we will work on computational models for human-microbe co-metabolism, which will allow in silico simulations of external influences, such as diet, at physiological scale. The research questions addressed by the core will mainly be driven by the three projects. To this end, we will focus on the blood-gut-brain axis in human omics datasets (project 1), in animal model datasets (project 3), and the effects of environment and diet on molecular phenotypes (project 2). A second, major focus of the core will be on the development and application of a microbiome-centric bioinformatic knowledge base (an ?atlas?). To this end, will construct a Neoj4-based network database integrating various heterogenous information, including results from metabolomics GWAS, eQTL studies, Alzheimer-phenotype related association studies (e.g. metabolomics biomarkers of AD endophenotypes), microbiome-metabolome associations etc. The atlas will allow us to answer complex research questions, such as finding the connections between a given set of metabolites, genes, metabolic pathways, GWAS hits, and AD endophenotypes in one single query. In the final part of this project, we will develop advanced network data mining algorithms on the atlas, to extract novel information beyond that of simple associations. This will lead to integrated molecular modules associated with AD, providing a multi-omics view on AD pathobiology. The core will be led by an experienced, international group of PIs with over a decade of experience in the field. The team has a track record in major fields of metabolic research, including diabetes, cancer, Alzheimer?s disease, microbiome analysis, and metabolic GWAS. In summary, the Computational and Systems Biology Core will be central element for computational approaches within the consortium, providing both data analysis and advanced data integration and data mining techniques.